TEL AVIV -- Family members of patients with brain cancer, particularly astrocytoma, may inherit a higher risk of the same diagnosis, researchers said.

Action Points

Explain to interested patients that brain cancer appears to have some degree of heritability.

Caution patients that the risk for relatives of brain cancer patients is small.

TEL AVIV, Sept. 22 -- Family members of patients with brain cancer, particularly astrocytoma, may inherit a higher risk of the same diagnosis, researchers said.

A first-degree relative with brain cancer more than tripled astrocytoma and glioblastoma risk for their family members, found Deborah T. Blumenthal, M.D., of Tel Aviv Sourasky Medical Center here, and Lisa A. Cannon-Albright, Ph.D., of the University of Utah in Salt Lake City.

In the large retrospective study, even second-degree relatives were at significantly elevated risk if a family member had astrocytoma (P=0.03), they reported in the Sept. 23 issue of Neurology.

Until now, oncologists have reassured patients that these cancers are not familial, she noted.

However, family members should not be overly concerned, Dr. Blumenthal emphasized. Familial gliomas are rare and accounted for less than 5% of brain cancer cases in their study, she said.

"It's still quite unlikely that direct family members will be diagnosed with these tumors as well," she cautioned. "These are not such strong links that we expect that if someone has it that their son or their grandson or their cousin is going to get it."

What it does mean is that physicians should have a lower threshold for evaluating symptoms in patients with a family history of brain cancer, she said.

However, "it's too early based on these kind of data to talk about prevention or even screening," Dr. Blumenthal said, and "the actual numbers are not large enough to warrant a complete change in how we look at these tumors."

The researchers used the Utah Population Database, which includes 10 generations of genealogy starting from the first white settlers, linked to Utah cancer registry records dating back to 1966.

The analysis included 1,401 primary astrocytoma and glioblastoma cases in these databases with at least three generations of genealogy available.

Among these cases, 38 had at least one first-degree relative also affected with a brain tumor. These cases came from 19 different brain tumor pedigrees or clusters, which "might be considered more likely to represent syndromic pedigrees," the researchers said.

Overall, the databases turned up 101 family lines with a high risk of brain cancer as indicated by at least three cases of astrocytoma or glioblastoma, significantly more than would be expected from chance.

A similar pattern was seen for brain cancers that struck at an early age, which the researchers noted is more common with cancers that have a genetic contribution compared with sporadic cases.

First-degree relatives of patients with brain cancer diagnosed before age 20 were at more than six times the risk of developing brain cancer than those without a family history (4 observed versus 0.6 expected, RR 6.44, P=0.004).

An early-onset case of astrocytoma in the family was associated with an even greater 9.65-fold elevation in risk for first-degree relatives (3 observed versus 0.3 expected, P=0.004), but no cases of early glioblastoma were seen in the databases to estimate this risk.

None of the cancer types alone or combined held significant risks for third-degree relatives.

Likewise, "relatedness" as measured by the Genealogical Index of Familiality for the tumor cases compared with controls were:

Significant for astrocytoma and glioblastoma considered together (3.01 versus 2.68, P=0.009)

Significant for astrocytoma overall (3.00 versus 2.44, P=0.008) with borderline significance for early cases as well (P=0.059)

Not significant for glioblastoma (3.09 versus 3.04, P=0.409)

Although these findings suggested only a nominal heritability component to glioblastoma, it's possible that a larger group of glioblastomas associated with environmental exposures is masking a true genetic component for a subset that results from transformation of astrocytoma to higher-grade tumors, the researchers said.

The significant elevation in glioblastoma risk in first-degree relatives may suggest this is the case, they noted.

The retrospective study could not definitively rule out a tumor predisposition syndrome as the cause of the associations found, the researchers cautioned.

However, if the majority of familial cases were "syndromic," a higher degree of clustering than observed would have been expected, they said.

The study was supported by funds from the National Institutes of Health, the Utah Department of Health, the University of Utah, and the University of Utah Huntsman Cancer Institute.

The researchers reported no conflicts of interest.

Reviewed by Zalman S. Agus, MD Emeritus Professor University of Pennsylvania School of Medicine